Sirtuin-Dependent Metabolic Control and Its Role in the Aging Process

During last years, the protein family of sirtuins, composed by NAD+-dependent deacetylases, has emerged as a key factor in aging. From yeast to humans, sirtuins are involved in metabolic changes that induce a higher respiratory capacity accompanied by lower oxidative damage. They are involved in the control of glucose catabolism, fatty acid metabolism, respiratory chain activity in mitochondria and several other metabolic processes including control of antioxidant capacity in cells and tissues (Dali-Youcef et al., 2007; Elliott & Jirousek, 2008; Lomb et al., 2010; Pallas et al., 2008). As these deacetylases are dependent on the NAD+/NADH ratio, they can be considered as important sensors of the metabolic status of the cells and probably because this they are one of the main family of proteins involved in the regulation of metabolism in the cell (Li & Kazgan, 2011). Further, their relationship with the AMPK-dependent pathway, that controls respiratory metabolism by inhibiting insulin-dependent signaling, highlights the importance of these proteins in metabolic regulation and especially in insulin-resistance, diabetes and obesity (Canto et al., 2009; Ruderman et al., 2010). Sirtuins have been involved in aging process and considered important factors in delaying aging process and increase longevity (Guarente, 2000; Tissenbaum & Guarente, 2001). However, very recent studies have questioned the role of these deacetylases in longevity (Burnett et al., 2011; Viswanathan & Guarente, 2011). But their activity in yeast, worms and flies still permits to correlate its function in metabolism and dietarydependent modulations with aging process (Guarente, 2008). However, to date, in mammals and, especially in humans, their role in longevity is not clear. Whereas in lower organisms only one member has been found, SIR2, in mammals, seven members have been described to date. This fact indicates a higher complexity in interactions, targets and functions in higher animals than in lowers. Further, in mammals, the specific distribution of these deacetylases among the different cell compartments also indicates several localdependent influences of sirtuins.